mCD99L2基因靶向siRNA诱导小鼠A20细胞转化为H/RS样细胞的实验研究
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摘要
研究背景
淋巴瘤是原发于淋巴造血组织的免疫系统恶性肿瘤，随着AIDS、器官移植、肿瘤放化疗免疫抑制的应用等近年来发病率急剧升高。引人关注的是霍奇金淋巴瘤(Hodgkin lymphoma，HL)独特的组织病理学特征，它虽是恶性淋巴瘤，但与非霍奇金淋巴瘤(non Hodgkin’s lymphoma，NHL)却截然不同：(1)HL的恶性细胞成分H／RS细胞一般只占肿瘤组织的极少部分(＜1％)，其余是大量以淋巴细胞为主的背景细胞；(2)随着病变发展H／RS细胞的数量增加，而背景细胞数目减少；(3)H／RS细胞不但在原发灶内与背景细胞同时存在，而且在扩散转移的病灶内也同时出现；(4)患者的预后与H／RS细胞数量呈负相关，而与背景细胞数量呈正相关，极少量的H／RS细胞却直接影响着HL的恶性程度与预后。令人费解的是如此少量的H／RS细胞是如何生存于大量背景细胞之中?它与背景细胞之间究竟存在怎样复杂的相互关系?它虽然失去表达免疫球蛋白的能力，但却能逃避凋亡而持续增生；H／RS细胞是如何发生、发展而来的?要探究这些悬而未解决的问题，当务之急是建立类似人HL病理特征的实验动物模型，动态观察H／RS细胞与背景细胞之间的相互作用，以揭示H／RS细胞生存、增殖、免疫逃避、免疫调节的机制。然而，迄今尚未有理
Introduction
Lymphomas are immune system malignant neoplasm of cells native to lymphoid tissue. Along with the widely use of immunosuppressant for AIDS, organ transplant, and chemotherapy for tumors, the occurrences of lymphomas have drastically increased in the recent years. Among all the research efforts in lymphomas, what have evoked great public interests are the unique histopathological characteristics of Hodgkin lymphoma (HL). Although both arise in the lymphoid tissue, Hodgkin's lymphoma is set apart from non Hodgkin's lymphomas by the following four distinctive areas in the lesions:
1. HL cells are made of a small number, less than < 1%, of H/RS cells, in a background with great majority of lymphocytes or background cells.
2. As the tumor progresses, the numbers of H/RS cells increase, while the background cells decrease.
3. H/RS cells not only co-exist with background cells in the primary location, but also appears in the destination where tumor metastases.
4. Prognosis of the tumor is negative correlated to the quantity of H/RS cells existing in the tumor and positive correlated to the background cells.
Apparently, this small amount of H/RS cells has directly impact on the degree of malignancy and prognosis. It is not very clear how this small quantity of H/RS cells can "survive" in the mass of background cells. They have lost their immunoglobulin presenting ability, but are capable of escaping apoptosis and continue growing. How
淋巴瘤是原发于淋巴造血组织的免疫系统恶性肿瘤，随着AIDS、器官移植、肿瘤放化疗免疫抑制的应用等近年来发病率急剧升高。引人关注的是霍奇金淋巴瘤(Hodgkin lymphoma，HL)独特的组织病理学特征，它虽是恶性淋巴瘤，但与非霍奇金淋巴瘤(non Hodgkin’s lymphoma，NHL)却截然不同：(1)HL的恶性细胞成分H／RS细胞一般只占肿瘤组织的极少部分(＜1％)，其余是大量以淋巴细胞为主的背景细胞；(2)随着病变发展H／RS细胞的数量增加，而背景细胞数目减少；(3)H／RS细胞不但在原发灶内与背景细胞同时存在，而且在扩散转移的病灶内也同时出现；(4)患者的预后与H／RS细胞数量呈负相关，而与背景细胞数量呈正相关，极少量的H／RS细胞却直接影响着HL的恶性程度与预后。令人费解的是如此少量的H／RS细胞是如何生存于大量背景细胞之中?它与背景细胞之间究竟存在怎样复杂的相互关系?它虽然失去表达免疫球蛋白的能力，但却能逃避凋亡而持续增生；H／RS细胞是如何发生、发展而来的?要探究这些悬而未解决的问题，当务之急是建立类似人HL病理特征的实验动物模型，动态观察H／RS细胞与背景细胞之间的相互作用，以揭示H／RS细胞生存、增殖、免疫逃避、免疫调节的机制。然而，迄今尚未有理
Introduction
Lymphomas are immune system malignant neoplasm of cells native to lymphoid tissue. Along with the widely use of immunosuppressant for AIDS, organ transplant, and chemotherapy for tumors, the occurrences of lymphomas have drastically increased in the recent years. Among all the research efforts in lymphomas, what have evoked great public interests are the unique histopathological characteristics of Hodgkin lymphoma (HL). Although both arise in the lymphoid tissue, Hodgkin's lymphoma is set apart from non Hodgkin's lymphomas by the following four distinctive areas in the lesions:
1. HL cells are made of a small number, less than < 1%, of H/RS cells, in a background with great majority of lymphocytes or background cells.
2. As the tumor progresses, the numbers of H/RS cells increase, while the background cells decrease.
3. H/RS cells not only co-exist with background cells in the primary location, but also appears in the destination where tumor metastases.
4. Prognosis of the tumor is negative correlated to the quantity of H/RS cells existing in the tumor and positive correlated to the background cells.
Apparently, this small amount of H/RS cells has directly impact on the degree of malignancy and prognosis. It is not very clear how this small quantity of H/RS cells can "survive" in the mass of background cells. They have lost their immunoglobulin presenting ability, but are capable of escaping apoptosis and continue growing. How
引文
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[1] Kuppers R and Hansmann ML. The Hodgkin and Reed/Stemberg cell [J]. IJBCB. 2005, 37(3): 511-517
[2] Lee IS, Kim SH, Song HG, et al.The molecular basis for the generation of Hodgldn and Reed-Sternberg cells in Hodgkin's lymphoma[J]. Int J Hematol. 2003, 77(4):330-5.
[3] 沈丽佳，何滢，蒋会勇，等．mic2／CD99在经典型霍奇金淋巴瘤H／RS细胞中的表达及与Eber-1／LMP-1相关性的研究[J]．中国病理生理杂志．2006，22(4)：766-780
[4] 沈丽佳，方唯意，谢思明，等．小鼠B淋巴瘤A20细胞株mCD99L2基因表达检测及真核表达载体的构建[J]．南方医科大学学报．200，26(2)：144-149
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